The human germline is essential for human reproduction. In women, loss of the germline is associated with primary ovarian insufficiency, premature ovarian aging, and reduced health span. To identify key determinants of human germline development, we use human tissues and stem cells combined with various genomics, transcriptomics, gene editing, and imaging approaches to advance our understanding of human germline development. Using human pluripotent stem cells and the specification of human germ cells in vitro, we show that human germ cell formation occurs in a niche enriched with extracellular matrix proteins and synergistic signaling between FGF2 and TGFβ. This niche creates competency for embryonic cells to respond to BMP4 and express the transcription factors TFAP2A and GATA3, which generates lineage-primed progenitors that undergo chromatin re-wiring to become enriched in transcription factor motifs for TFAP2A and GATA3. It is upon this regulatory landscape germ cell specification occurs through the induction of SOX17 and up-regulation of TFAP2C. In the absence of FGF and TGFβ1 signaling, cells lose the competency to become human germ cells and instead differentiate into TFAP2C-expressing amnion cells. In the absence of TFAP2A, germ cell formation is significantly compromised, with amnion specification mostly unaffected. In summary, utilizing human pluripotent stem cells, we are gaining a deeper understanding of the niche and gene regulatory requirements for the specification of human germ cells and therefore a deeper understanding of what makes us human.